Geographical Patterns and Risk Factor Association of Cardio-Oncology Mortality in the United States.

Cardio-oncology mortality (COM) is a complex issue that is compounded by multiple factors that transcend a depth of socioeconomic, demographic, and environmental exposures. Although metrics and indexes of vulnerability have been associated with COM, advanced methods are required to account for the intricate intertwining of associations. This cross-sectional study utilized a novel approach that combined machine learning and epidemiology to identify high-risk sociodemographic and environmental factors linked to COM in United States counties. The study consisted of 987,009 decedents from 2,717 counties, and the Classification and Regression Trees model identified 9 county socio-environmental clusters that were closely associated with COM, with a 64.1% relative increase across the spectrum. The most important variables that emerged from this study were teen birth, pre-1960 housing (lead paint indicator), area deprivation index, median household income, number of hospitals, and exposure to particulate matter air pollution. In conclusion, this study provides novel insights into the socio-environmental drivers of COM and highlights the importance of utilizing machine learning approaches to identify high-risk populations and inform targeted interventions for reducing disparities in COM.

Ruptured mycotic coronary artery aneurysm.

Aneurysms complicated by rupture of the coronary arteries are exceedingly rare. Literature regarding management of mycotic aneurysms resulting in rupture is limited. Therefore, we describe a fascinating diagnosis, imaging progression and management of a ruptured mycotic coronary artery aneurysm.

Heroin Use Is Associated With Vascular Inflammation in Human Immunodeficiency Virus.

BACKGROUND: Heroin use may work synergistically with human immunodeficiency virus (HIV) infection to cause greater immune dysregulation than either factor alone. Unraveling how this affects end-organ disease is key as it may play a role in the excess mortality seen in people with HIV (PWH) who use heroin despite access to care and antiretroviral therapy. METHODS: This is a prospectively enrolled, cross-sectional study of adults with and without HIV who use and do not use heroin using (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to compare tissue-specific inflammation including aortic (target-to-background ratio [TBR]), splenic, and bone marrow (standardized uptake value [SUV]). RESULTS: A total of 120 participants were enrolled. The unadjusted mean difference in aortic TBR was 0.43 between HIV-positive [HIV+] heroin+ and HIV+ heroin-negative [heroin-] (P = .02); however, among HIV-, aortic TBR was similar regardless of heroin-use status. Further, HIV-by-heroin-use status interaction was significant (P = .02), indicating that the relationship between heroin use and higher aortic TBR depended on HIV status. On the other hand, both HIV (1.54 vs 1.68; P = .04, unadjusted estimated means for HIV+ vs HIV-) and heroin use were associated with lower bone marrow SUV, although the effect of heroin depended on sex (heroin-use-by-sex interaction, P = .03). HIV-by-heroin-use interaction was not significant for splenic or bone marrow SUV. CONCLUSIONS: Aortic inflammation was greatest in PWH who use heroin, but paradoxically, bone marrow activity was the least in this group, suggesting complex and possibly divergent pathophysiology within these different end organs.

Examining Disparities and Excess Cardiovascular Mortality Before and During the COVID-19 Pandemic.

OBJECTIVE: To investigate the patterns and demographic features of cardiovascular disease (CVD) death and subtypes myocardial infarction (MI), stroke, and heart failure in the pre-COVID-19 era (2018-2019) vs during the COVID-19 pandemic (2020-2021) in the United States. METHODS: In this cross-sectional study, we used the US Multiple Cause of Death files for 2018 to 2021 to examine the trend of excess cause-specific deaths using International Classification of Diseases, Tenth Revision codes for CVD (I00 to I99), MI (I21 and I22), stroke (I60 to I69), and heart failure (I42 and I50). Our primary outcome was excess mortality from CVD and its 3 subtypes (MI, stroke, and heart failure) between prepandemic (2018-2019) and pandemic (2020-2021) years. We performed a subgroup analysis on race and month-to-month and year-to-year variation using χ2 analysis to test statistical significance. RESULTS: Overall, 3,598,352 CVD deaths were analyzed during the study period. There was a 6.7% excess CVD mortality, 2.5% MI mortality, and 8.5% stroke mortality during the COVID-19 pandemic (2020-2021) compared with the prepandemic era (2018-2019). Black individuals had higher excess CVD mortality (13.8%) than White individuals (5.1%; P<.001). This remained consistent across subtypes of CVD, including MI (9.6% vs 1.0%; P<.001), stroke (14.5% vs 6.9%; P<.001), and heart failure (5.1% vs -1.2%; P<.001). CONCLUSION: There has been a significant rise in CVD and subtype-specific mortality during the COVID-19 pandemic that has been persistent despite 2 years since the onset of the pandemic. Excess CVD mortality has disproportionately affected Black compared with White individuals. Further studies targeting and eliminating health care disparities are necessary.

Prevalence of thoracic aortic aneurysm in patients referred for no/low-charge coronary artery calcium scoring: Insights from the CLARIFY registry.

Objective: Low-dose cardiac-gated chest CTs allow for simultaneous evaluation of coronary artery calcification and aortic size. We sought to evaluate the prevalence of thoracic aortic dilation (TAD) and thoracic aortic aneurysm (TAA) in a large cohort of patients undergoing coronary artery calcium (CAC) screening. Methods: We reviewed all patients from a large, prospective no-charge CAC screening program (CLARIFY, Clinicaltrials.gov NCT04075162) for whom measurements of the ascending aorta were available. TAD was defined as an ascending aortic diameter ≥4.0cm, while TAA was defined as ascending aortic diameter ≥ 4.5cm. We explored associations between patient characteristics, CAC, and the prevalence of TAD/TAA. Results: A total of 36,356 patients enrolled in the CLARIFY program underwent analysis for TAD/TAA. 3,130 patients (8.6%) had TAD and 237 (0.7%) had TAA. Patients with TAA were older (63±8 vs 59±10 years, p < 0.001), more likely to be male (87% vs 49%, p < 0.001), have higher BMI (32 vs 30 kg/m2, p < 0.001), and 10-year atherosclerotic cardiovascular disease estimated risk (18% vs 12%, p < 0.001). Similar differences were observed for individuals with TAD compared to individuals without TAD with respect to age (63 vs 59 years, p < 0.001), percent male (76% vs 46%, p < 0.001), BMI (32 vs 30 kg/m2, p < 0.001), and 10-year predicted risk (17% vs 11%, p < 0.001). CAC score was associated with prevalence of TAD (4.9% in those with CAC 0 to 16.5% in those with CAC≥400) and TAA (0.3% in those with CAC of 0 to 1.5% in those with CAC ≥400). Conclusion: In this large, prospective study of patients undergoing no-charge CAC screening, 8.6% had TAD (≥4.0cm) and 0.7% had TAA (≥4.5cm). Our results highlight a high yield of TAD/TAA diagnosis in this targeted cohort with cardiovascular risk factors and supports the role of no-charge CAC as a population-level strategy.

Reported Pericardial Toxicities Associated with Acute Myelogenous Leukemia Treatments: A Pharmacovigilance Analysis of the FDA Adverse Reporting Database.

Acute myelogenous leukemia (AML) is one of the most common leukemias experienced in adults and conveys significant morbidity and mortality. While the traditional anthracycline based treatments of AML involves cytarabine, developments in alternatives (liposomal cytarabine, fludarabine, cladribine, azacitidine, decitabine), and targeted agents (midostaurin, gilteritinib, enasidenib, ivosidenib, gemtuzumab ozogamicin, and venetoclax) exist. Multiple cardiovascular adverse events, notably pericardial toxicity, have been observed in small studies; however, to date little is known about the comparative pericardial toxicity among these newer regimens. Due to the paucity of data, we sought to investigate the reported pericardial events and mortality associated with treatments for AML. Utilizing the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), we identified all adverse events associated with FDA approved treatments for AML (2002-2022). Pericardial events were defined as pericarditis, pericardial effusion and tamponade. We excluded any individuals with age <18 years old. Logistic regression was utilized to identify factors associated with pericardial events. Out of 94,262 reported adverse events, 675 pericardial toxicities were included (243 pericarditis, 479 tamponade). Pericardial events occurred less often in Cladribine (0.3%, P < 0.001), fludarabine (0.4%, P < 0.001), Venetoclax (0.3%, P < 0.001), enasidenib (0.3%, P value < 0.001), and ivosidenib (0.3%, P < 0.001) compared to Cytarabine (0.9%). Tamponade events occurred significantly less often in cladribine (0.1%, P < 0.001), fludarabine (0.4%, P = 0.001), enasidenib (0.1%, P = 0.006), ivosidenib (0.1%, P = 0.01), and venetoclax (0.1%, P < 0.001) compared to cytarabine 0.7%. After adjusting for age and sex, Cladribine (reporting odds ratio [ROR] 0.35 [95% CI 0.18-0.68], P = 0.008) and Fludarabine (ROR 0.65 [0.45-0.92], P = 0.03), venetoclax (ROR 0.57 [0.41-0.79], P < 0.001) remained significantly associated with lower incidence of reported pericardial events. While cytarabine has been the routinely used and/or drug of choice for induction chemotherapy for AML, alternatives like cladribine may have a greater safety profile regarding pericardial toxicities. Future studies should be directed at further investigating cardiovascular safety profiles of AML induction therapy.

Proportionate and Absolute Vascular Disease Mortality by Race and Sex in the United States From 1999 to 2019.

Background Despite the known significant morbidity and mortality associated with cardiovascular disease and peripheral vascular disease (PVD), contemporary data describing racial demographics in PVD mortality are scarce. Methods and Results Using the multiple causes of death file from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research, we analyzed the trends of age-adjusted mortality (AAMR) for PVD and its subtypes (aortic aneurysm/dissection, arterial thrombosis, venous thrombosis/disease, pulmonary embolism), by race and sex between 1999 and 2019. Of the 17 826 871 deaths attributed to cardiovascular disease, a total of 888 187 (5.0%) PVD deaths were analyzed during the study period (12.4% Black, 85.6% White). Between 1999 and 2019, AAMR for PVD decreased by 52% (24.8-11.8 per 100 000 people) in the overall population. Despite a decrease in the overall mortality across all race and sex groups, Black men and Black women continued to have higher mortality for PVD (1.5×), aortic dissection (1.8×), arterial thrombosis (1.3×), and venous thrombosis/disease (2.0×) mortality compared with White men and White women in 2019. While there was a 53% decrease in PVD among White individuals (AAMR 24.5-11.5 per 100 000), there was only a 43% decrease (30.0-17.1) in PVD AAMR in Black individuals between 1999 and 2019. The ratio of PVD AAMR increased from 1.2 (1999) to 1.5 (2019) in Black men/White men and from to 1.3 (1999) to 1.5 (2019) in Black women/White women. Similar trends were noted in aortic dissection (Black men/White men, 1.2-1.8; and Black women/White women, 1.5-1.7), arterial thrombosis (Black men/White men, 1.0-1.3; and Black women/White women, 0.9-1.3), and venous thrombosis/disease (Black men/White men, 1.7-1.8; and Black women/White women, 1.7-2.0). Conclusions In this retrospective review of death certificate data in the United States, we demonstrate continued significant disparities between Black and White populations in PVD mortality and its subtypes. Future studies should investigate etiologies and social determinants of PVD mortality.

Multi-variable biomarker approach in identifying incident heart failure in chronic kidney disease: results from the Chronic Renal Insufficiency Cohort study.

AIMS: Heart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality in the ever-growing population of patients with chronic kidney disease (CKD). There is a need to enhance early prediction to initiate treatment in CKD. We sought to study the feasibility of a multi-variable biomarker approach to predict incident HF risk in CKD. METHODS AND RESULTS: We examined 3182 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) without prevalent HF who underwent serum/plasma assays for 11 blood biomarkers at baseline visit (B-type natriuretic peptide [BNP], CXC motif chemokine ligand 12, fibrinogen, fractalkine, high-sensitivity C-reactive protein, myeloperoxidase, high-sensitivity troponin T (hsTnT), fibroblast growth factor 23 [FGF23], neutrophil gelatinase-associated lipocalin, fetuin A, aldosterone). The population was randomly divided into derivation (n = 1629) and validation (n = 1553) cohorts. Biomarkers that were associated with HF after adjustment for established HF risk factors were combined into an overall biomarker score (number of biomarkers above the Youden's index cut-off value). Cox regression was used to explore the predictive role of a biomarker panel to predict incident HF. A total of 411 patients developed incident HF at a median follow-up of 7 years. In the derivation cohort, four biomarkers were associated with HF (BNP, FGF23, fibrinogen, hsTnT). In a model combining all four biomarkers, BNP (hazard ratio [HR] 2.96 [95% confidence interval 2.14-4.09]), FGF23 (HR 1.74 [1.30-2.32]), fibrinogen (HR 2.40 [1.74-3.30]), and hsTnT (HR 2.89 [2.06-4.04]) were associated with incident HF. The incidence of HF increased with the biomarker score, to a similar degree in both derivation and validation cohorts: from 2.0% in score of 0% to 46.6% in score of 4 in the derivation cohort to 2.4% in score of 0% to 43.5% in score of 4 in the validation cohort. A model incorporating biomarkers in addition to clinical factors reclassified risk in 601 (19%) participants (352 [11%] participants to higher risk and 249 [8%] to lower risk) compared with clinical risk model alone (net reclassification improvement of 0.16). CONCLUSION: A basic panel of four blood biomarkers (BNP, FGF23, fibrinogen, and hsTnT) can be used as a standalone score to predict incident HF in patients with CKD allowing early identification of patients at high-risk for HF. Addition of biomarker score to clinical risk model modestly reclassifies HF risk and slightly improves discrimination.

Case series of closure devices complications.

Vascular closure devices (VCD) are effective at achieving hemostasis. VCD failure is attributed to underlying arterial disease, leading to a hazardous situation for obtaining contralateral femoral access. Radial-to-peripheral (R2P) access has emerged as a safe option to rescue these procedural complications. Here, we present two cases of VCD failure rescue utilizing R2P and outline this approach step-by-step.

Inflammatory Markers and Risk of Heart Failure With Reduced to Preserved Ejection Fraction.

Chronic systemic inflammation is associated with an increased risk of heart failure (HF). We sought to determine the association between biomarkers of systemic inflammation interleukin (IL)-6, IL-2, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) with those of HF and its subtypes. We hypothesize that inflammatory biomarkers IL-6, IL-2, TNF-α, and CRP are associated with HF and its subtypes. We included participants from the Multi-Ethnic Study of Atherosclerosis (a prospective population-based cohort study [2000 to 2002]), without a history of HF, and with available baseline inflammatory biomarkers. We explored the association of IL-6, IL-2, TNF-α, and CRP with incident HF, HF with reduced ejection fraction (left ventricular ejection fraction [LVEF] <40%, HFrEF), HF with midrange EF (LVEF 40% to 50%, HFmrEF), and HF with preserved ejection fraction (LVEF >50%, HFpEF). Among 6,814 participants, 195 developed HF over 10.9 years (56 HFrEF, 30 HFmrEF, and 57 HFpEF). In the models adjusted for clinical risk factors of HF, IL-6 (hazard ratio [HR] 1.33 per doubling; 95% confidence interval [CI] 1.10 to 1.60), TNF-α (HR 2.49 per doubling; 95% CI 1.18 to 5.28), and CRP (HR 1.18 per doubling; 95% CI 1.06 to 1.30) were associated with all HF, and IL-6 (HR 1.51 per doubling; 95% CI 1.09 to 2.10) and CRP (HR 1.21 per doubling; 95% CI: 1.01 to 1.45) were associated with incident HFpEF, whereas none of the examined biomarkers were associated with HFmrEF or HFrEF. In conclusion, inflammatory biomarkers (IL-6, TNF-α, and CRP) are independently associated with incident HF. IL-6 and CRP are associated with incident HFpEF but not HFrEF or HFmrEF. These findings suggest that activation of the IL-6/CRP pathway (as cause, consequence, or epiphenomenon) may be unique to HFpEF.

Proportionate Cardiovascular Mortality in Chronic Inflammatory Disease in Adults in the United States From 1999 to 2019.

BACKGROUND: Despite a rising prevalence of chronic inflammatory disease (CID), the recent trends in cardiovascular disease (CVD) mortality of patients with CID is scarce. In this study, we investigated patterns of CVD mortality in systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA) compared with the general population. METHODS: We used the 1999 to 2019 multiple causes of death files from the national center for health statistics to analyze patterns and trends of proportionate CVD mortality in CID compared with the general population. RESULTS: We analyzed a total of 11,154 CVD deaths in IBD, 58,337 CVD deaths in RA, 6227 CVD deaths in SLE, and 17,826,871 CVD deaths in the general population. Between 1999 and 2019, we found that proportionate CVD mortality decreased significantly in the IBD group (25% to 16%), RA group (34% to 25%), and the general population (41% to 31%), but did not change for the SLE group (15% to 15%). Patients with SLE who died of CVD were approximately 10 years younger compared with CVD decedents with RA, IBD, or general population. The White population had higher proportionate CVD mortality than African American (IBD [19% vs 16%-18%] and SLE [14%-16% vs 12-14%], respectively). CONCLUSIONS: This study identifies current trends in CVD mortality in the CID population and elucidates current demographics in CVD mortality in CID. Although proportionate CVD mortality decreased in the general population, and in patients with RA and IBD, there was no change among patients with SLE. Further studies are needed to elucidate these differences.

Non-invasive Imaging in the Evaluation of Cardiac Allograft Vasculopathy in Heart Transplantation: A Systematic Review.

Cardiac allograft vasculopathy (CAV) is the leading cause of long-term graft dysfunction in patients with heart transplantation and is linked with significant morbidity and mortality. Currently, the gold standard for diagnosing CAV is coronary imaging with intravascular ultrasound during traditional invasive coronary angiography. Invasive imaging, however, carries increased procedural risk and expense to patients in addition to requiring an experienced interventionalist. With the improvements in non-invasive cardiac imaging modalities such as transthoracic echocardiography, computed tomography, magnetic resonance imaging and positron emission tomography, an alternative non-invasive imaging approach for the early detection of CAV may be feasible. In this systematic review, we explored the literature to investigate the utility of non-invasive imaging in diagnosis of CAV in >3000 patients across 49 studies. We also discuss the strengths and weaknesses for each imaging modality. Overall, all 4 imaging modalities show good to excellent accuracy for identifying CAV with significant variations across studies. Majority of the studies compared non-invasive imaging with invasive coronary angiography without intravascular imaging. In summary, non-invasive imaging modalities offer an alternative approach to invasive coronary imaging for CAV. Future studies should investigate longitudinal non-invasive protocols in low-risk patients after heart transplantation.